The effects of different levels of crude protein (CP) and cottonseed meal replacing for soybean meal in cassava chips and rice straw-based diets for mid-lactating cows (100-150 day in milk [DIM]), were studied using 32 multiparous Holstein Fresian crossbred dairy cows. Diets containing 10.5, 12.5, 13.7, 14.4% CP of the rations and 0, 12.1, 14.9, 17.8% cottonseed meal were fed to cows for 60 days. Thirty two cows were randomly divided into four dietary treatments using a Randomized complete block design. Four dietary treatments were offered in the form of total mixed ration (TMR) with concentrate to roughage (chopped rice straw) at 60:40 and offered ad libitum. Dry matter (DM) and neutral detergent fiber (NDF) intakes tended to linearly increase with increasing dietary CP levels. Intakes and digestibility of crude protein increased linearly with increasing dietary CP level (p<0.01). Crude protein digestibility of the 10.5% CP diet was lower (p<0.05) than that in diets with higher levels of CP, while there were no significant differences among the other three levels of CP (12.5, 13.7 and 14.4%). Daily milk yield tended to increase with increased CP from 10.5 to 14.4%. Income over feed in terms of US$/kg of milk increased with increased CP from 10.5 to 13.7% and decreased when the CP level was higher than 13.7% (quadratic effect p<0.09). Milk composition was not significantly affected by increasing level of CP, however there were relatively high contents of protein and fat among treatments. The proportion of milk-urea N (MUN), ammonia-N (NH3-N) and blood-urea N (BUN) were closely correlated and increased linearly with increasing CP levels (p<0.01). Balanced diet was found in diet containing 12.5 and 13.7% CP of the rations when BUN and MUN were used as indicators of the protein to energy ratio in the diet. Conclusions can be made that increasing dietary CP levels from 10.5 to 13.7% using cottonseed meal as the main source to completely replace soybean meal was beneficial to cows consuming rice straw and cassava chips based-diets. Increasing the CP level above 13.7% of total ration did not additionally improve milk yield and composition or net income.